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THYROID PEROXIDASE ISOFORM A
LATEST LITERATURE
1: Applied ergonomics, 2010 Aug 12, 34(9)
Reducing understaffing and shift work with Temporal Profile Optimization (TPO).
[Abstract]The ergonomic quality of shift schedules can be improved by reducing time periods with understaffing (resulting in work-pressure, poor quality, etc.) and evening, night and/or weekend work. Improving the quality of forecasts regarding future workforce requirements as well as the optimization of work processes by moving as much work as possible to more suitable time zones are two approaches to this. We introduce and propose Temporal Profile Optimization (TPO) as a systematic approach to question the demand as well as its translation to workforce planning. Temporal profiles describe the number of employees needed over time (e.g. for different days of the week, times of day, for different calendar days) as well as the shift-times and staffing levels planned to meet this workforce demand. With Temporal Profile Forecasts we introduce a forecasting method that is based on time-stamped historical data and methodologically supplements traditional time series models like SARIMA in many ways. With Temporal Profile Reengineering we use systematic and often participatory methods from business process reengineering to identify moveable work and streamline the load lines by (re-)distributing movable work such that shifts and schedules are improved. The approach is illustrated along two business cases. Using TP-Forecasts for air traffic controllers increased forecasting accuracy whereby a different shift design was possible resulting in 3-4% less shift work. In a warehouse of an Austrian freight carrier a TP-Forecast together with TP-Reengineering helped to rearrange work processes such that the resulting workforce requirements curve had a more even form. This allowed for shorter shifts than before (thereby decreasing overtime). Experiences made so far stress the potential of Temporal Profile Optimization.
2: Journal of pediatric endocrinology & metabolism : JPEM, 2009 Sep, 22(9)
Final diagnosis in children with subclinical hypothyroidism and mutation analysis of the thyroid peroxidase gene (TPO).
[Abstract]AIM: To determine the final diagnosis of patients with subclinical hypothyroidism (SCH), and to perform mutation screening of the thyroid peroxidase gene (TPO). METHODS: Infants with SCH without an identified etiology were included in the study. Patients with thyroid dysgenesis were excluded. Children > or = 2 years of age, and still on L-thyroxine (LT4) treatment underwent a diagnostic algorithm. After LT4 was discontinued for 4 weeks, thyroid function tests (TFT) were obtained. A perchlorate discharge test (PDT) was performed in patients with normal thyroid ultrasound but abnormal TFT. Sequence analysis of TPO was studied in all children who underwent a PDT. RESULTS: Forty-eight patients (23 males and 25 females) completed the trial. Among these children, 19 (39.5%) had transient SCH, and 29 (60.5%) had permanent SCH. Among patients with permanent SCH, 19 had thyroid hypoplasia, six had partial iodide organification defect with positive PDT, and four had other dyshormonogenesis with negative PDT. Mean LT4 dose before the medication ceased was 1.2 +/- 0.5 microg/kg/day in transient cases, and 1.7 +/- 0.4 in those with permanent SCH (p < 0.05). No TPO mutation was detected. However, in five patients, seven different previously known TPO polymorphisms were detected: c.102C > G, L4L; > A, A576A; c.2088C > T, D666D; c.2263A > C, T725P; c.2630 T >C, V847A. CONCLUSIONS: LT4 treatment should be stopped after the age of 2 years in infants with SCH without a definite pathology of the thyroid gland to exclude cases with transient hypothyroidism. Additionally, we should consider particularly thyroid gland hypoplasia, and also partial defects in iodide organification in infants with SCH.
3: Blood, 2009 Oct 29, 114(18)
TPO-mimetics and myelofibrosis? A reticulin question!
[Abstract]
4: Biochemical and biophysical research communications, 2009 Oct 23,
Neuropilin-1 forms complexes with vascular endothelial growth factor receptor-2 during megakaryocytic differentiation of UT-7/TPO cells.
[Abstract]We investigated whether the gene expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR and neuropilin-1 [NRP-1]) could be specifically regulated during the megakaryocytic differentiation of human thrombopoietin (TPO)-dependent UT-7/TPO cells. Undifferentiated UT-7/TPO cells expressed a functional VEGFR-2, leading to VEGF binding and VEGF(165)-induced tyrosine phosphorylation, cell proliferation, and apoptosis inhibition. The megakaryocytic differentiation of UT-7/TPO cells on treatment with phorbol myristate acetate (PMA) was accompanied by a marked up-regulation of NRP-1 mRNA and protein expression and by an increase in VEGF-binding activity, which was mainly mediated by VEGFR-2. VEGF(165) promoted the formation of complexes containing NRP-1 and VEGFR-2 in undifferentiated UT-7/TPO cells in a dose-dependent manner. Unlike human umbilical vein endothelial cells, PMA-differentiated UT-7/TPO cells exhibited complex formation between NRP-1 and VEGFR-2 even in the absence of VEGF(165). These findings suggest that NRP-1-VEGFR-2-complex formation may contribute to effective cellular functions mediated by VEGF(165) in megakaryocytic cells.
5: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2009 Jul 30, 32(10)
Is an upper limit of 2.5 mUI/l for TSH appropriate for the first trimester of pregnancy among young TPO - women?
[Abstract]Objectives. The general purpose of this study is to assess the distribution among the various hormonal indices in young pregnant women with negative thyroid peroxidase antibodies and iodine sufficiency and classify them accordingly while comparing them to literature proposed reference values for the first trimester. Methods. A sectional study was carried out, including 127 pregnant women enrolled at the prenatal outpatient clinic at the Nova Iguacu General Hospital, in the period comprised between 2000 and June 2007. They were submitted to TSH, free T(4), total T(4), TBG, and thyroid peroxidase antibody determinations. Results. A median equal to 38.7 mug/ml was observed for TBG; TSH values varied between 0.02 and 5.84 mcUI/ml, with a median of 1.25 mcUI/ml. For total T(4) and free T(4), median values were, respectively 10.3 mug/dl and 1.20 ng/dl. Thirteen patients out of 115 displayed a TSH serum level above 2.5 mUI/ml. Conclusions. Patients with subclinical hypothyroidism classified by this new cutoff (serum TSH concentration between 2.5 mUI/l and the upper limit of the reference range), chiefly ATPO-negative young women display no need for treatment as there is no evidence that this condition is associated with maternal and fetal complications.
6: Diabetes care, 2009 Oct, 32(10)
Graves hyperthyroidism after stopping immunosuppressive therapy in type 1 diabetic Islet cell recipients with pretransplant TPO autoantibodies.
[Abstract]OBJECTIVE: After an initially successful islet cell transplantation, a number of patients return to C-peptide negativity, and therefore immunosuppressive therapy is discontinued. Some are then found to have developed Graves disease. We examined the risk of Graves disease after immunosuppression. RESEARCH DESIGN AND METHODS: Immunosuppressive therapy was stopped in 13 type 1 diabetic islet cell recipients who had received one course of antithymocyte globulin and maintenance doses of mycophenolate mofetil and a calcineurin inhibitor. None had a history of thyroid disease. RESULTS: In four patients, clinical Graves hyperthyroidism was observed within 21 months after discontinuation and 30-71 months after the start of immunosuppressive therapy. All four patients exhibited a pretransplant positivity for thyroid peroxidase (TPO) autoantibodies, while the nine others were TPO negative pre- and posttransplantation. CONCLUSIONS: Type 1 diabetic recipients of islet cell grafts with pretransplant TPO autoantibody positivity exhibit a high risk for developing Graves hyperthyroidism after immunosuppressive therapy is discontinued for a failing graft.
7: Bioorganic & medicinal chemistry letters, 2008 Oct 1, 18(19)
Optimization of small molecule agonists of the thrombopoietin (Tpo) receptor derived from a benzo[a]carbazole hit scaffold.
[Abstract]The lead optimization of a novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported. The chemical instability of the dihydro-benzo[a]carbazole lead 2 was successfully addressed in the design and evaluation of compounds which also demonstrated improved potency compared to 2. Members of the scaffold have been identified which are full agonists that demonstrate cellular functional potency <50 nM. Analog 21 demonstrates equivalent efficacy in the human megakaryocyte differentiation (CFU-mega) assay compared to Eltrombopag.
8: Blood, 2008 Sep 15, 112(6)
TPO signaling: when the tyrosines go marching in(side).
[Abstract]The lead optimization of a novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported. The chemical instability of the dihydro-benzo[a]carbazole lead 2 was successfully addressed in the design and evaluation of compounds which also demonstrated improved potency compared to 2. Members of the scaffold have been identified which are full agonists that demonstrate cellular functional potency <50 nM. Analog 21 demonstrates equivalent efficacy in the human megakaryocyte differentiation (CFU-mega) assay compared to Eltrombopag.
9: Bioorganic & medicinal chemistry letters, 2008 Oct 1, 18(19)
Discovery and biological evaluation of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor.
[Abstract]A novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported. Starting from a 3.4 microM high throughput screen hit, members of this series have been identified which are full agonists with functional potency <50 nM and oral bioavailability in mice.
10: Fertility and sterility, 2008 Sep 5, 18(19)
Increased fetal abortion rate in autoimmune thyroid disease is related to circulating TPO autoantibodies in an autoimmune thyroiditis animal model.
[Abstract]OBJECTIVE: To determine the fertility and abortion rates in a mouse model of autoimmune thyroiditis and its relationship with circulating anti-thyroid peroxidase (TPO) antibody. DESIGN: Experimental animal study. SETTING: University research laboratory. ANIMAL(S): C57bl/6 mice. INTERVENTION(S): Female C57bl/6 mice immunized with recombinant mouse TPO (rmTPO) in complete Freund adjuvant (CFA) or glutathione-S-transferase (GST-CFA) were allowed to mate. The pregnant mice were killed on day 14 of pregnancy for assessment of fetal development. The effects of TPO antibody on preimplantation embryo development and implantation rate were also studied. MAIN OUTCOME MEASURE(S): Litter size, resorption rate, preimplantation embryo development, and implantation rate. RESULT(S): All of the mice immunized with rmTPO-CFA possessed anti-TPO antibody. They had reduced litter size and increased incidence of resorbed fetus compared with the control. Higher serum TSH levels, but not T(4) levels, were demonstrated after rmTPO-CFA immunization. Anti-TPO antibody bound to preimplantation embryos. Treatment of the embryos with the antibody marginally decreased the formation of 3/4-cell embryos but had no effect on the subsequent development and implantation compared with the nonimmune control sera. CONCLUSION(S): Autoimmune thyroiditis is associated with reduced fertility and higher incidence of fetal loss. The anti-TPO antibody may affect post-implantation embryo development, leading to fetal loss.
11: Experimental hematology, 2008 Sep, 36(9)
Analysis of the temporal and concentration-dependent effects of BMP-4, VEGF, and TPO on development of embryonic stem cell-derived mesoderm and blood progenitors in a defined, serum-free media.
[Abstract]OBJECTIVE: To develop a robust serum-free (SF) system for generation of hemogenic mesoderm and blood progenitors from pluripotent cells. MATERIALS AND METHODS: Embryonic stem cells (ESCs) maintained in N2B27 supplemented with leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP)-4 were induced to differentiate into Brachyury/T-expressing cells (measured using a green fluorescent protein reporter) and myeloid-erythroid colony-forming cells (ME-CFCs), by removing LIF, changing the base media formulation, and via the time- and concentration-dependent addition of other factors. RESULTS: Presence of 10 ng/mL BMP-4 permitted the emergence of cells expressing T and the vascular endothelial growth factor receptor (VEGFR)-2, however, <5% of the cells were double-positive on day 4. Adjusting the SF media formulation allowed only 5 ng/mL BMP-4 to yield 24% +/- 4% Brachyury-green fluorescent protein VEGFR-2(+) cells by day 4. These cells could develop into ME-CFC, producing 4.4 +/- 0.8 CFC per 1000 cells at day 8. We also examined the timing and concentration sensitivity of BMP-4, VEGF, and thrombopoietin (TPO) during differentiation. BMP-4 with 50 ng/mL TPO generated 232 +/- 48 CFC per 5 x 10(4) cells, similar to the serum-control, and this response could be enhanced to 292 +/- 42 CFC per 5 x 10(4) cells by early (between day 0-5), but not late (after day 5) VEGF treatment. CONCLUSION: Moving to SF systems facilitates directed differentiation by eliminating confounding signals. This article describes modifications to the N2B27 media that amplify mesoderm induction and extends earlier work defining blood progenitor cell induction from ESC with BMP-4, VEGF, and TPO.
12: International journal of hematology, 2008 Jul, 88(1)
Thrombopoietin (TPO) regulates HIF-1alpha levels through generation of mitochondrial reactive oxygen species.
[Abstract]Hypoxia inducible factor (HIF)-1 is a master transcriptional regulator mediating the cellular adaptation to hypoxia. In addition, HIF-1 is also vital for the development of hematopoietic stem cells (HSCs). In a previous study we found that thrombopoietin (TPO), an important and non-redundant cytokine for HSC maintenance and expansion, induces HIF-1alpha expression in HSCs by enhancing the stability of HIF-1alpha under normoxic conditions. However, the molecular mechanisms of these effects are not yet fully understood. In this study, we explored the mechanisms and found that TPO-induced mitochondrial reactive oxygen species (ROS) played a crucial role in stabilization of HIF-1. Both ROS scavengers and inhibitors of mitochondrial electron transport completely blocked HIF-1alpha induction by TPO in UT-7/TPO cells and in primary immature mouse bone marrow cells. We also found that TPO-induced HIF-1alpha induction was tightly coupled with glucose metabolism. Inhibition of glucose transporter or glycolytic enzyme blocked HIF-1alpha elevation of TPO. These results indicate that TPO induces HIF-1alpha expression in a manner very similar to that of hypoxia.
13: Ugeskrift for laeger, 2008 Apr 28, 170(18)
[Thyroid papillary cancer using TPO staining]
[Abstract]Immunostaining for TPO (MoAb47) has been used to predict the risk of thyroid cancer in thyroid adenomas without uptake in thyroid 99m pertechnetate scintigraphy. This case describes a 16-year-old girl with thyroid papillary cancer staining 95% positive using TPO staining. The case indicates that TPO staining can not be used as the only parameter in the evaluation of the risk of cancer in the thyroid gland.
14: International journal of medical sciences, 2008, 5(2)
TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders.
[Abstract]Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.
15: Critical reviews in oncology/hematology, 2008 Mar, 65(3)
TPO-independent megakaryocytopoiesis.
[Abstract]Megakaryocytopoiesis is a continuous developmental process of platelet production. In this process, a complex network of hemopoietic growth factors are involved, among which TPO (thrombopoietin) is the most thoroughly investigated regulator of MKs (megakaryocytes). In addition to TPO, other regulators also have non-negligible effects on megakaryocytopoiesis. The majority of their effects are independent of TPO signaling. To date, TPO-independent megakaryocytopoiesis forms a regulatory system that includes four signals and (an) unknown signaling pathway(s). These four pathways are the gp 130 (glycoprotein 130)-dependent signaling pathway, the Notch pathway, NMDA (N-methyl-d-aspartate) receptor-mediated signaling, and the SDF-1 (stromal cell-derived factor-1)/FGF-4 (fibroblast growth factor-4) paradigm. Understanding of the TPO-independent regulatory system is important because the system may offer additional opportunities to understand the developmental process and the mechanisms of disorders characterized by abnormal MK and platelet production, such as thrombocytopenia and thrombocythemia, and to advance the development of therapeutics.
16: Clinical endocrinology, 2007 Dec, 67(6)
Factors associated with elevated serum concentrations of anti-TPO antibodies in subjects with and without diffuse goitre. Results from the Ukrainian-American Cohort Study of thyroid cancer and other thyroid diseases following the Chornobyl accident.
[Abstract]OBJECTIVES: To examine factors associated with the prevalence of elevated anti-thyroid peroxidase antibodies (ATPO) among iodine-deficient adolescents and young adults and test whether associations vary according to the presence of diffuse goitre. DESIGN: Subjects were members of the Ukrainian-American Cohort Study exposed to the Chornobyl accident whose (131)I thyroid dose estimates were below 0.2 Gy. MEASUREMENTS: The odds ratios (ORs) for ATPO above 60 U/ml were estimated using logistic regression models for a number of factors in the total population (N = 5133), and separately for thyroid disease-free subjects (N = 3875), those with diffuse goitre (N = 921), and diffuse goitre without autoimmune thyroiditis (AIT; N = 883). RESULTS: Elevated ATPO was found in 9.9% of the total population and ORs were significantly higher in females, older individuals, those examined in earlier calendar years, residents of Kyiv and Chernihiv oblasts, subjects with a family history of thyroid disease, higher thyroid ultrasound volume, suppressed or elevated TSH, blood collection in March to May, very low thyroglobulin (Tg), and shorter serum storage time. When thyroid disease-free subjects and those with diffuse goitre were compared, there were few differences in antibody prevalence, and after excluding individuals with AIT, the only difference was an increased prevalence of elevated ATPO at low urinary iodine in those with goitre alone. CONCLUSIONS: Although a number of factors are associated with the prevalence of elevated ATPO in our study group, with the exception of urinary iodine these factors are independent of goitre, and differences between thyroid disease-free subjects and those with diffuse goitre are largely due to AIT.
17: Clinical endocrinology, 2008 Jun, 68(6)
Immunohistochemical staining for thyroid peroxidase (TPO) of needle core biopsies in the diagnosis of scintigraphically cold thyroid nodules.
[Abstract]BACKGROUND: Cold thyroid nodules are common, in particular in iodine-deficient areas, but only a minority of them are malignant requiring surgery. Thyroid peroxidase (TPO) immunostaining of fine-needle aspiration cytology (FNAC) material has proven helpful in diagnosing cells from malignant lesions, but the procedure has its limitations in a routine setting. PURPOSE: To improve diagnosis and reduce surgery rate, the FNAC procedure was replaced by needle core biopsy (NCB), which was routinely stained for TPO by the monoclonal antibody mAb 47. MATERIALS AND METHODS: During a 5-year period 427 consecutive patients with a cold thyroid nodule were evaluated by ultrasound-guided NCB, which had been routinely stained for TPO in an automated immunostainer. Sensitivity and specificity and predictive values of the TPO immunostaining were estimated, based on the final diagnosis obtained from surgical resection. RESULTS: The majority of nodules with benign NCB diagnosis were not surgically removed, and thus a subgroup of 140 operated nodules formed the basis for the calculations. Sensitivity and specificity for benign and malignant lesions were 100% if the oxyphilic variant of adenomas and minimally invasive follicular carcinomas were excluded. By inclusion of these, the values fell to 89% and 97%, respectively. The predictive value of a positive test was 96% and the predictive value of a negative test was 97%. CONCLUSION: TPO immunostaining was found to be a valuable adjunct to morphology in the diagnosis of cold thyroid nodules of the nonoxyphilic type.
18: The Journal of clinical endocrinology and metabolism, 2008 Feb, 93(2)
Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations: molecular and in silico studies.
[Abstract]CONTEXT AND OBJECTIVE: Most cases of goitrous congenital hypothyroidism (CH) from thyroid dyshormonogenesis 1) follow a recessive mode of inheritance and 2) are due to mutations in the thyroid peroxidase gene (TPO). We report the genetic mechanism underlying the apparently dominant inheritance of goitrous CH in a nonconsanguineous family of French Canadian origin. DESIGN, SETTING, AND PARTICIPANTS: Two brothers identified by newborn TSH screening had severe hypothyroidism and a goiter with increased (99m)Tc uptake. The mother was euthyroid, but the father and two paternal uncles had also been diagnosed with goitrous CH. After having excluded PAX8 gene mutations, we hypothesized that the underlying defect could be TPO mutations. RESULTS: Both compound heterozygous siblings had inherited a mutant TPO allele carried by their mother (c.1496delC; p.Pro499Argfs2X), and from their father, one brother had inherited a missense mutation (c.1978C-->G; p.Gln660Glu) and the other an insertion (c.1955insT; p.Phe653Valfs15X). The thyroid gland of one uncle who is a compound heterozygote for TPO mutations (p.Phe653Valfs15X/p.Gln660Glu) was removed because of concurrent multiple endocrine neoplasia type 2A. Immunohistochemistry revealed normal TPO staining, implying that Gln660Glu TPO is expressed properly. Modeling of this mutant in silico suggests that its three-dimensional structure is conserved, whereas the electrostatic binding energy between the Gln660Glu TPO and its heme group becomes repulsive. CONCLUSION: We report a pedigree presenting with pseudodominant goitrous CH due to segregation of three different TPO mutations. Although goitrous CH generally follows a recessive mode of inheritance, the high frequency of TPO mutations carriers may lead to pseudodominant inheritance.
19: Journal of translational medicine, 2007, 5(6)
Optimal ex vivo expansion of neutrophils from PBSC CD34+ cells by a combination of SCF, Flt3-L and G-CSF and its inhibition by further addition of TPO.
[Abstract]BACKGROUND: Autologous mobilised peripheral blood stem cell (PBSC) transplantation is now a standard approach in the treatment of haematological diseases to reconstitute haematopoiesis following myeloablative chemotherapy. However, there remains a period of severe neutropenia and thrombocytopenia before haematopoietic reconstitution is achieved. Ex vivo expanded PBSC have been employed as an adjunct to unmanipulated HSC transplantation, but have tended to be produced using complex cytokine mixtures aimed at multilineage (neutrophil and megakaryocyte) progenitor expansion. These have been reported to reduce or abrogate neutropenia but have little major effect on thrombocytopenia. Selective megakaryocyte expansion has been to date ineffective in reducing thrombocytopenia. This study was implemented to evaluate neutrophil specific rather than multilineage ex vivo expansion of PBSC for specifically focusing on reduction or abrogation of neutropenia. METHODS: CD34+ cells (PBSC) were enriched from peripheral blood mononuclear cells following G-CSF-mobilisation and cultured with different permutations of cytokines to determine optimal cytokine combinations and doses for expansion and functional differentiation and maturation of neutrophils and their progenitors. Results were assessed by cell number, morphology, phenotype and function. RESULTS: A simple cytokine combination, SCF + Flt3-L + G-CSF, synergised to optimally expand and mature neutrophil progenitors assessed by cell number, phenotype, morphology and function (superoxide respiratory burst measured by chemiluminescence). G-CSF appears mandatory for functional maturation. Addition of other commonly employed cytokines, IL-3 and IL-6, had no demonstrable additive effect on numbers or function compared to this optimal combination. Addition of TPO, commonly included in multilineage progenitor expansion for development of megakaryocytes, reduced the maturation of neutrophil progenitors as assessed by number, morphology and function (respiratory burst activity). CONCLUSION: Given that platelet transfusion support is available for autologous PBSC transplantation but granulocyte transfusion is generally lacking, and that multilineage expanded PBSC do not reduce thrombocytopenia, we suggest that instead of multilineage expansion selective neutrophil expansion based on this relatively simple cytokine combination might be prioritized for development for clinical use as an adjunct to unmanipulated PBSC transplantation to reduce or abrogate post-transplant neutropenia.
20: Clinical endocrinology, 2007 Jun, 66(6)
Ethnic differences in TSH but not in free T4 concentrations or TPO antibodies during pregnancy.
[Abstract]OBJECTIVE: To describe the TSH, free T4 and thyroid peroxidase antibody (TPO-Ab) concentrations during pregnancy among four ethnic groups and to determine reference values for these parameters during normal pregnancy. METHODS: Cross-sectional study of a cohort of 3270 pregnant women living in the city of Amsterdam. Blood samples were drawn at first booking in the first or second trimester. TSH, free T4 and TPO-Ab concentrations were determined. Four ethnic groups were studied: Dutch, Surinam, Turkish and Moroccan. RESULTS: Plasma TSH increased and free T4 decreased from the first to the second trimester of pregnancy for all the ethnic groups. Ethnic differences were observed in TSH concentrations, with Dutch females having the highest TSH levels compared to the other three ethnic groups. The median TSH difference was 0.16 mU/l between the Dutch and Moroccan women, 0.15 mU/l between the Dutch and Surinam women and 0.10 mU/l between the Dutch and Turkish women. These could not be explained by differences in age, parity and current smoking status. No differences were seen in free T4 concentrations between the four ethnic groups. The prevalence of TPO-Ab was comparable across the ethnic groups (about 6% in each); the concentration of TPO-Ab was also comparable among the ethnic groups. The Dutch women had a higher lower-limit (2.5 percentile) of the TSH reference range than the Surinam, Turkish and Moroccan women, ranging from 0.14 mU/l for the Surinam and Moroccan to 0.27 mU/l for the Dutch women. CONCLUSION: The increase in TSH and decrease in free T4 values during pregnancy correspond to previous reported studies. Pregnant Dutch women had consistently higher TSH values than the ethnic group, but corresponding free T4 levels and TPO-Ab did not differ between these ethnic groups.